Abstract
The adapter SLP-76 is essential for thymocyte development. SLP-76(-/-) mice were reconstituted with SLP-76 deletion mutant transgenes to examine the role of SLP-76 domains in T cell development and function. The N-terminal domain deletion mutant completely failed to restore thymocyte development. Mice reconstituted with Gads-binding site and SH2 domain deletion mutants had decreased thymic cellularity, impaired transition from double to single positive thymocytes, and decreased numbers of mature T cells in the spleen. Calcium mobilization and extracellular signal-regulated protein kinase activation were decreased in the Gads-binding site mutant but almost normal in the SH2 domain mutant. T cells from both mutants failed to proliferate following T cell antigen receptor ligation. Nevertheless, both mutants mounted partial cutaneous hypersensitivity responses and normal T cell dependent IgG1 antibody responses. These results indicate differential roles for SLP-76 domains in T cell development, proliferation and effector functions.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adaptor Proteins, Signal Transducing
-
Animals
-
Antigens, CD / metabolism
-
Antigens, Differentiation, T-Lymphocyte / metabolism
-
Binding Sites / genetics
-
Calcium / metabolism
-
Cell Differentiation
-
Cell Division
-
Isoenzymes / metabolism
-
Lectins, C-Type
-
Lymphocyte Activation
-
Mice
-
Mice, Knockout
-
Mice, Transgenic
-
Mitogen-Activated Protein Kinases / metabolism
-
Mutation
-
Ovalbumin / immunology
-
Phospholipase C gamma
-
Phosphoproteins / chemistry
-
Phosphoproteins / genetics
-
Phosphoproteins / immunology*
-
Protein Structure, Tertiary
-
Receptors, Antigen, T-Cell, alpha-beta / metabolism
-
Receptors, Interleukin-2 / metabolism
-
Sequence Deletion
-
T-Lymphocytes / cytology
-
T-Lymphocytes / immunology*
-
Type C Phospholipases / metabolism
-
src Homology Domains
Substances
-
Adaptor Proteins, Signal Transducing
-
Antigens, CD
-
Antigens, Differentiation, T-Lymphocyte
-
CD69 antigen
-
Isoenzymes
-
Lectins, C-Type
-
Phosphoproteins
-
Receptors, Antigen, T-Cell, alpha-beta
-
Receptors, Interleukin-2
-
SLP-76 signal Transducing adaptor proteins
-
Ovalbumin
-
Mitogen-Activated Protein Kinases
-
Type C Phospholipases
-
Phospholipase C gamma
-
Calcium